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Platelet-Derived TGF (Transforming Growth Factor)-ß1 Enhances the Aerobic Glycolysis of Pulmonary Arterial Smooth Muscle Cells by PKM2 (Pyruvate Kinase Muscle Isoform 2) Upregulation.
Zhu, Ying; Shu, Dan; Gong, Xue; Lu, Meng; Feng, Qinyu; Zeng, Xiang-Bin; Zhang, Han; Gao, Jiahui; Guo, Ya-Wei; Liu, Luman; Ma, Rong; Zhu, Liping; Hu, Qinghua; Ming, Zhang-Yin.
Afiliação
  • Zhu Y; Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China (Y.Z., D.S., X.G., M.L., X.-B.Z., J.G., Y.W.G., L.L., R.M., Z.-Y.M.).
  • Shu D; The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China (Y.Z., D.S., X.G., M.L., X.-B.Z., J.G., Y.W.G., L.L., R.M., Z.-Y.M.).
  • Gong X; Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China (Y.Z., D.S., X.G., M.L., X.-B.Z., J.G., Y.W.G., L.L., R.M., Z.-Y.M.).
  • Lu M; The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China (Y.Z., D.S., X.G., M.L., X.-B.Z., J.G., Y.W.G., L.L., R.M., Z.-Y.M.).
  • Feng Q; Department of Pharmacy, School of Medicine, Wuhan University of Science and Technology, Wuhan, China (D.S.).
  • Zeng XB; Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China (Y.Z., D.S., X.G., M.L., X.-B.Z., J.G., Y.W.G., L.L., R.M., Z.-Y.M.).
  • Zhang H; The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China (Y.Z., D.S., X.G., M.L., X.-B.Z., J.G., Y.W.G., L.L., R.M., Z.-Y.M.).
  • Gao J; Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China (Y.Z., D.S., X.G., M.L., X.-B.Z., J.G., Y.W.G., L.L., R.M., Z.-Y.M.).
  • Guo YW; The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China (Y.Z., D.S., X.G., M.L., X.-B.Z., J.G., Y.W.G., L.L., R.M., Z.-Y.M.).
  • Liu L; Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China (Y.Z., D.S., X.G., M.L., X.-B.Z., J.G., Y.W.G., L.L., R.M., Z.-Y.M.).
  • Ma R; The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China (Y.Z., D.S., X.G., M.L., X.-B.Z., J.G., Y.W.G., L.L., R.M., Z.-Y.M.).
  • Zhu L; Department of Gastroenterology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China (Q.F.).
  • Hu Q; Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China (Y.Z., D.S., X.G., M.L., X.-B.Z., J.G., Y.W.G., L.L., R.M., Z.-Y.M.).
  • Ming ZY; The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan, China (Y.Z., D.S., X.G., M.L., X.-B.Z., J.G., Y.W.G., L.L., R.M., Z.-Y.M.).
Hypertension ; 79(5): 932-945, 2022 05.
Article em En | MEDLINE | ID: mdl-35232222
BACKGROUND: Metabolic reprogramming is a hallmark of pulmonary arterial hypertension. Platelet activation has been implicated in pulmonary arterial hypertension (PAH), whereas the role of platelet in the pathogenesis of PAH remains unclear. METHODS: First, we explored the platelet function of semaxanib' a inhibitor of VEGF receptor (SU5416)/hypoxia mice and monocrotaline-injected rats PAH model. Then we investigated pulmonary arterial smooth muscle cell aerobic glycolysis after being treated with platelet supernatant. TGF (transforming growth factor)-ßRI, pyruvate kinase muscle 2, and other antagonists were applied to identify the underlying mechanism. In addition, platelet-specific deletion TGF-ß1 mice were exposed to chronic hypoxia and SU5416. Cardiopulmonary hemodynamics, vascular remodeling, and aerobic glycolysis of pulmonary arterial smooth muscle cell were determined. RESULTS: Here, we demonstrate that platelet-released TGF-ß1 enhances the aerobic glycolysis of pulmonary arterial smooth muscle cells after platelet activation via increasing pyruvate kinase muscle 2 expression. Mechanistically, platelet-derived TGF-ß1 regulate spyruvate kinase muscle 2 expression through mTOR (mammalian target of rapamycin)/c-Myc/PTBP-1(polypyrimidine tract binding protein 1)/hnRNPA-1(heterogeneous nuclear ribonucleoprotein A1) pathway. Platelet TGF-ß1 deficiency mice are significantly protected from SU5416 plus chronic hypoxia-induced PAH, including attenuated increases in right ventricular systolic pressure and less pulmonary vascular remodeling. Also, in Pf4cre+ Tgfb1fl/fl mice, pulmonary arterial smooth muscle cells showed lower glycolysis capacity and their pyruvate kinase muscle 2 expression decreased. CONCLUSIONS: Our data demonstrate that TGF-ß1 released by platelet contributes to the pathogenesis of PAH and further highlights the role of platelet in PAH.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Hipertensão Arterial Pulmonar / Hipertensão Pulmonar Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Hipertensão Arterial Pulmonar / Hipertensão Pulmonar Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article